This study involved the induction of septic arthritis in chimpanzees with strains of M. hominis and U. urealyticum and with a pathogenic strain of M. pneumoniae. An acute septic arthritis was experimentaly induced in chimpanzees inoculated intraarticularly with strains of Mycoplasma hominis and Ureaplasma urealyticum, each isolated from a patient with septic arthritis. The disease induced was similar to that observed in patients with regard to clinical signs of disease, degree of colonization, and the extent of the inflammatory and antibody responses produced. A very large inoculum of the arthritogenic Mycoplasma hominis strain 1620 given intravenously or of the non-cytadsorbing laboratory reference type strain PG21 given intraarticularly produced no overt clinical disease. U. urealyticum serovar SVII strain 2010B isolated from the septic joint of a patient with hypogammaglobulinema and in low broth passage produce severe disease, whereas the laboratory reference Serovar SVII type strain OC in high passage produced mild disease. Whereas the arthritogenic Ureaplasma strain produced an intense inflammatory response and a weak metabolism inhibition antiboey response, the high passage laboratory type strain produced a mild arthritis and minimal inflammation but a greater metabolism inhibition antibody response. Thus the source of the original isolate, attentuation of virulence by continuous broth passage and the ability to attach may all be important factors in determining the ability of Mycoplasmas to experimentally induce arthritic disease.